US6964772B1 - Chitosan-xanthan based polyionic hydrogels for stabilization and controlled release of vitamins - Google Patents
Chitosan-xanthan based polyionic hydrogels for stabilization and controlled release of vitamins Download PDFInfo
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- US6964772B1 US6964772B1 US09/301,670 US30167099A US6964772B1 US 6964772 B1 US6964772 B1 US 6964772B1 US 30167099 A US30167099 A US 30167099A US 6964772 B1 US6964772 B1 US 6964772B1
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- hydrogel
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- xanthan
- vitamins
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- 239000000017 hydrogel Substances 0.000 title claims abstract description 59
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Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
- A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
- A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
- A23L33/15—Vitamins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
- A61K31/07—Retinol compounds, e.g. vitamin A
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/365—Lactones
- A61K31/375—Ascorbic acid, i.e. vitamin C; Salts thereof
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L5/00—Compositions of polysaccharides or of their derivatives not provided for in groups C08L1/00 or C08L3/00
- C08L5/08—Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
- A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
- A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs
Definitions
- the present invention relates to chitosan/xanthan based hydrogels. More specifically, the present invention deals with chitosan/xanthan based hydrogels used in dermatology and as food additives, where such hydrogels are used as carrier for active compounds such as vitamins, amino-acids, nucleic acids, polypeptides, etc.
- One of the key aspects in the preparation of food additives and dermatological preparations is the preservation of active ingredients prone to degradation, such as vitamins, amino-acids, nucleic acids and polypeptides. Exposure of such ingredients to heat or light accelerates their degradation.
- thermo- or photo sensitive active ingredients such as vitamins, nucleic acids, amino-acids and polypeptides.
- An object of the present invention is therefore to provide a hydrogel preparation for use as a delivery device for food or dermatological preparations with a concurrent objects of providing stabilization of thermo- and photo sensitive active ingredients and avoiding any irritation or toxicity potentials.
- a further object of the present invention is to disclose a method of dispersion of the active ingredient within the hydrogel matrix.
- thermo- and photo sensitive bioactive molecules there is provided a preparation which stabilises thermo- and photo sensitive bioactive molecules.
- the preparation comprises a hydrogel made of a complex of chitosan and xanthan. Within the hydrogel there is lodged at least one thermo- or photo sensitive substance chosen among the following: vitamins, amino-acids, nucleic acids and polypeptides.
- the hydrogel configuration and structure is prepared so as to release, in a controlled way, the thermo- or photo sensitive ingredients either in a human or animal subjects.
- the present invention also discloses a method of making these hydrogels.
- the present invention also teaches the use of these hydrogels in dermatology or as a food additive vehicle.
- FIG. 1 is a complex of chitosan and xanthan
- FIG. 2 is a diagram of the lab apparatus for kinetic studies
- FIG. 3 is an amount of Vitamin C released as a function of time/ Sample coded VS2L.
- the hydrogel CHITOXANTM —Vitamin C is prepared with CHITOXANTM having a swelling index ( ⁇ ) of 1800%;
- FIG. 4 is the rate of release of Vitamin C as a function of time. Sample coded VS2L;
- FIG. 5 is the amount of Vitamin C released as a function of time/ Sample coded VS2R.
- the hydrogel CHITOXANTM —Vitamin C is prepared with CHITOXANTM having a swelling index ( ⁇ ) of 2200%;
- FIG. 6 is the rate of release of Vitamin C as a function of time. Sample coded VS2R; and
- FIG. 7 is the variation of the % of Vitamin C released as a function of time.
- the hydrogel CHITOXANTM —Vitamin C is prepared with CHITOXANTM having a swelling index ( ⁇ ) of 3500%.
- compositions for food and dermatological applications comprising one or several active ingredients that are either prone to thermo- or photo degradation.
- These compositions are based on a polyionic hydrogels obtained by a chitosan/ xanthan complexing which incorporates therein the active ingredients thereby protecting them from thermo- or photo induced degradation while controlling their release thus enhancing their activity and the duration of this activity.
- liposoluble active ingredients are introduced in the hydrogel during the making of the hydrogel.
- hydrosoluble active ingredients are introduced by diffusion in the already made hydrogel. Both methods can be used in sequence.
- the present invention thus reveals a novel and surprising way of introducing various vitamins and other ingredients such as amino-acids, nucleic acids and polypeptides in hydrogels and of controlling the release of those ingredients in various drug delivery vehicles such as: capsules or gelcaps for oral ingestion, rectal suppositories, creams and ointments, gels, solutions and cutaneous patches.
- various drug delivery vehicles such as: capsules or gelcaps for oral ingestion, rectal suppositories, creams and ointments, gels, solutions and cutaneous patches.
- the present invention further reveals a method of introducing in the same hydrogel liposoluble and hydrosoluble active ingredients.
- the present invention further discloses methods of making food additives and dermatological creams incorporating the hydrogel.
- dermatologic and “dermatological” are used in their widest sense thus covering both the dermatological and cosmetic applications. Furthermore, these terms are meant to cover direct skin treatments or treatment through nails or hair.
- food additive is also to be understood in its widest sense including thus all food preparations where the additive has a nutritional or therapeutic function as well as simple mechanical functions such as that of a texturizing agent, filler or viscosity control agent.
- the preparations covered by the present invention focus mainly on humans although they may be used in the veterinary field.
- the hydrogel of the present invention is an ionic complex between chitosan, a cationic natural polymer, and xanthan, an anionic natural polymer.
- a method of making of the hydrogel has been described in U.S. Pat. No. 5,720,206 granted to the same assignee as in the present application and is incorporated herein by reference.
- xanthan and chitosan form a complex, i.e. a network of ionic linkages between these two polymer molecules.
- the complex is a highly hydrophilic hydrogel.
- Vitamin A also called Retinol
- Retinol is a molecule extremely sensitive to light and oxygen. As a consequence, this vitamin may not be used in a cream unless it is being stabilised to counteract the negative effects of light and oxygen (from ambient air).
- the method of the present invention consists in stabilising Vitamin A in a hydrogel made of xanthan and chitosan complex. The xanthan and chitosan complex being described in U.S. Pat. No. 5,620,706.
- a solution (100 ml) of Vitamin A (10-20 w/v %) in ethanol is first prepared. This solution is added, under intense agitation, to 500 ml of a xanthan solution, 0.65 w/v %. The final solution has a Vitamin A concentration between 1.66 and 3.33 w/v %. The solution is kept at 3° C. It is subsequently sprayed, via a nozzle, into 800 ml of a 0.65 w/v % chitosan solution. The complexation reaction is conducted during 30 minutes. The gel formed is then filtered and rinsed with water to a pH of 6.8.
- the final product can be freeze dried and has 46 mg of Vitamin A per g of freeze dried xanthan-chitosan complex.
- the method (a) developed for Vitamin A is also applied for the inclusion of Vitamin E.
- the concentration of Vitamin E in the freeze dried hydrogel can reach 20 wt %.
- the method (a) developed for Vitamin A is also applied for the inclusion of Vitamin K.
- the concentration of Vitamin K in the freeze dried hydrogel can reach 20 wt %.
- the diffusion method in the freeze dried hydrogel to avoid loss of ingredients that would otherwise occur during the reaction between xanthan and chitosan.
- the xanthan-chitosan hydrogel must have a swelling index of at least 2000%.
- Step 1 Preparation of the xanthan-chitosan complex (CHITOXANTM), i.e. the polyonic hydrogel;
- Step 2 Incorporation of Vitamin C.
- Step 1 follows the method described in U.S. Pat. No. 5,620,706.
- Chitosan used has typically a molecular weight comprised between 250,000 and 350,000 and the hydrogel produced a swelling index of ⁇ >2000%.
- the CHITOXANTM thus produced is milled to obtain a fine powder of particles comprised between 250 and 500 ⁇ m.
- This step can be carried out via two different approaches:
- Vitamin C thus incorporated in the freeze-dried hydrogel and hydrated shows a good stability, without coloration after 2 weeks at 45° C. (wet hydrogel) and after 20 weeks at 45° C. (dried hydrogel). It is also possible to use as “stabilisers” either tartaric acid at 0.1 wt %, metaphosphoric acid at 0.03 wt % or citric acid at 0.1 wt %. The percentage is expressed with respect to CHITOXANTM.
- the previous method (2a) is used replacing the three amino-acids with a tripeptide having sulfur-containing functionalities.
- g of Vitamin C and 0.002 g of glutathione are added.
- 1 g of CHITOXANTM is added.
- the mixture is kept in slight agitation until a homogeneous paste is obtained.
- the mixture is left to stand for 2 hours to reach the equilibrium hydration.
- the paste is then frozen and freeze-dried. All operations preferably require absence of light.
- the solvent used is an aqueous mixture of 3% (w/v) metaphosphoric acid and 8% (v/v) acetic acid.
- the method consists of introducing 20 to 30 mg of freeze-dried CHITOXANTM loaded with Vitamin C in a 50 ml centrifuge tube together with 40 ml of the extraction solvent. The mixture is magnetically stirred for 60 minutes. The suspension formed is centrifuged (4000 rpm) and the supernatant is analysed. All operations are done in absence of light.
- the calibration curve is constructed at 243 nm as follows. A solution of 1.3 mg/ml of Vitamin C in the solvent is prepared in a graduated cylinder. The solution is prepared just before analysis. By successive dilutions, the absorption versus concentration calibration curve (mg/ml) is thus measured.
- the concentration of Vitamin C in the supernatant obtained via extraction is determined at 243 nm using the calibration curve.
- the concentration of Vitamin C in the sample prepared by method 2a is 49.6%.
- CHITOXANTM 1 g
- C preparation is hydrated with water until a creamy paste is obtained. Weighing the paste permits to calculate the amount of Vitamin C present. Subsequently, the paste is mixed, under strong agitation, with a base cream in order to achieve a final concentration in Vitamin C preferably comprised between 5 and 25 wt %.
- Table 1 shows the types of CHITOXANTM —Vit. C combinations studied. As illustrated in FIG. 2 , the controlled release kinetics is determined by introducing a precise quantity of the CHITOSANTM —Vit. C preparation in the reactor.
- the solvent a mixture of 3% w/v methaphosphoric acid and 8% w/v acetic acid, flows into the central tube directly into the reactor where it comes into contact with the CHITOXANTM —Vit. C preparation.
- the Vitamin C is gradually released from the preparation and solubilizes inside the solvent. The latter leaves the reactor through small orifices ensuring constant circulation of the solvent and good contact with the preparation.
- FIG. 3 shows that the Vitamin C released from sample VS2L follows a linear increase as a function of time with two distinct slopes, depicted in FIG. 4 .
- FIG. 4 shows that with sample VS2L, the Vitamin C diffuses at a constant speed of 0.36 mg/min during the first period while it decreases by half for the 100 following minutes.
- Sample VS2R also shows in FIG. 5 the two distinct linear increase profiles with two distinct slopes depicted in FIG. 6 .
- the first slope is faster than that of preparation VS2L indicating a more rapid liberation.
- the second slope at 0.02 mg/min, releases Vitamin C at a controlled but slow rate.
- FIG. 7 shows the liberation of Vitamin C for preparation VS2M. The release of 85% of the Vitamin C is achieved in the first 10 min.
- the physical characteristics of the chitosan-xanthan hydrogel will determine the structure and more or less viscous texture of the final products.
- the choice of a hydrogel as described in the present invention will permit to adapt the hydrogel to diversified food applications.
- the present invention also covers the production of tablets using CHITOXANTM —Vit. C powder and other active ingredients as well when required.
- tablets made of freeze-dried powder of other chitosan- xanthan hydrogels containing different vitamins, amino-acids, nucleic acids and polypeptides and their combinations can be prepared.
Abstract
Description
α=100% X mass of swelled hydrogel in equilibrium−mass of dried hydrogel mass of dried hydrogel
Under these conditions, the time for the experiment is decreased thereby preventing the molecule's degradation. The method involves dissolving 0.07 g of Vitamin A in 1 ml of ethanol (96%) and adding 1.5 g of the freeze dried xanthan-chitosan complex having α=2500%. Slight agitation allows the obtention of a homogeneous paste. 2 ml of ethanol, and 200 μl of water are then added under slight agitation and the mixture is kept at 4° C. for 24 hours in absence of light. The alcohol is then evaporated, at 4° C. The final product can be freeze dried and has 46 mg of Vitamin A per g of freeze dried xanthan-chitosan complex.
-
- 2a. Stabilisation with amino-acids
-
- 2b. Stabilisation with tripeptides
TABLE 1 |
Types of CHITOXAN ™ - Vit. C preparations studied |
Preparations Codes | Swelling index (α) | Concentration of Vit. C in |
CHITOXAN ™ - | of CHITOXAN ™ | the CHITOXAN ™ - Vit. C |
Vit. C | % | (wt %) |
VS2L | 1800 | 50.3 |
VS2R | 2200 | 49.6 |
VS2M | 3500 | 51.0 |
Claims (9)
Applications Claiming Priority (1)
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CA002243619A CA2243619A1 (en) | 1998-07-17 | 1998-07-17 | Chitosan- and xanthan-based polyionic hydrogels for the stabilization and controlled release of vitamins |
Publications (1)
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US6964772B1 true US6964772B1 (en) | 2005-11-15 |
Family
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US09/301,670 Expired - Fee Related US6964772B1 (en) | 1998-07-17 | 1999-04-28 | Chitosan-xanthan based polyionic hydrogels for stabilization and controlled release of vitamins |
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US (1) | US6964772B1 (en) |
EP (1) | EP1098931B1 (en) |
AT (1) | ATE225822T1 (en) |
AU (1) | AU4765999A (en) |
CA (1) | CA2243619A1 (en) |
DE (1) | DE69903436T2 (en) |
ES (1) | ES2185367T3 (en) |
WO (1) | WO2000004086A1 (en) |
Cited By (7)
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US20080213334A1 (en) * | 2006-09-29 | 2008-09-04 | Lockwood Nathan A | Polyelectrolyte media for bioactive agent delivery |
US8710107B2 (en) | 2006-04-05 | 2014-04-29 | Woodland Biofuels Inc. | System and method for converting biomass to ethanol via syngas |
US8795727B2 (en) | 2009-11-09 | 2014-08-05 | Spotlight Technology Partners Llc | Fragmented hydrogels |
US9314441B2 (en) | 2011-10-19 | 2016-04-19 | R.P. Scherer Technologies, Llc | Two phase pharmaceutical delivery system |
US9700650B2 (en) | 2009-11-09 | 2017-07-11 | Spotlight Technology Partners Llc | Polysaccharide based hydrogels |
JP2021080228A (en) * | 2019-11-22 | 2021-05-27 | 株式会社アンズコーポレーション | Method for suppressing coloring of oil-soluble vitamin and cosmetics |
CN115090225A (en) * | 2022-05-12 | 2022-09-23 | 重庆中科力泰高分子材料股份有限公司 | Novel efficient aldehyde-removing transparent gel and preparation method thereof |
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BR0112258A (en) * | 2000-07-07 | 2003-06-24 | Kemestrie Inc | Poorly Water Soluble Drug Delivery System |
ATE390127T1 (en) * | 2003-09-01 | 2008-04-15 | Jpm The Jordanian Pharmaceutic | UNIVERSAL COMPOSITION FOR CONTROLLED ACTIVE ACTIVE DELIVERY CONTAINING CHITOSAN |
CN1307253C (en) * | 2005-02-03 | 2007-03-28 | 徐放 | Chitosan water-retaining gel adhesive substrate materials and method for preparing same |
DE102008048227A1 (en) | 2008-09-18 | 2010-04-01 | Friedrich-Schiller-Universität Jena | Producing polyelectrolyte hydrogel bodies, useful e.g. as soft tissue implants, comprises filling a semi-permeable membrane-forming liquid and a coagulation medium in a hollow template to form hollow semipermeable membrane body |
IT1403064B1 (en) * | 2010-11-18 | 2013-10-04 | Mangiapane | COMPOSITION OF SUBSTANCES FOR THE TREATMENT OF PATIENTS WITH HYPERCOLESTEROLEMIA AND RELATED PATHOLOGIES |
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- 1999-07-16 DE DE69903436T patent/DE69903436T2/en not_active Expired - Fee Related
- 1999-07-16 AU AU47659/99A patent/AU4765999A/en not_active Abandoned
- 1999-07-16 EP EP99930966A patent/EP1098931B1/en not_active Expired - Lifetime
- 1999-07-16 WO PCT/CA1999/000651 patent/WO2000004086A1/en active IP Right Grant
- 1999-07-16 AT AT99930966T patent/ATE225822T1/en not_active IP Right Cessation
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US8710107B2 (en) | 2006-04-05 | 2014-04-29 | Woodland Biofuels Inc. | System and method for converting biomass to ethanol via syngas |
US20080213334A1 (en) * | 2006-09-29 | 2008-09-04 | Lockwood Nathan A | Polyelectrolyte media for bioactive agent delivery |
US8795727B2 (en) | 2009-11-09 | 2014-08-05 | Spotlight Technology Partners Llc | Fragmented hydrogels |
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US9700650B2 (en) | 2009-11-09 | 2017-07-11 | Spotlight Technology Partners Llc | Polysaccharide based hydrogels |
US9861701B2 (en) | 2009-11-09 | 2018-01-09 | Spotlight Technology Partners Llc | Hydrogel compositions |
US10159742B2 (en) | 2009-11-09 | 2018-12-25 | Spotlight Technology Partners Llc | Hydrogel compositions |
US9314441B2 (en) | 2011-10-19 | 2016-04-19 | R.P. Scherer Technologies, Llc | Two phase pharmaceutical delivery system |
JP2021080228A (en) * | 2019-11-22 | 2021-05-27 | 株式会社アンズコーポレーション | Method for suppressing coloring of oil-soluble vitamin and cosmetics |
CN115090225A (en) * | 2022-05-12 | 2022-09-23 | 重庆中科力泰高分子材料股份有限公司 | Novel efficient aldehyde-removing transparent gel and preparation method thereof |
Also Published As
Publication number | Publication date |
---|---|
EP1098931B1 (en) | 2002-10-09 |
DE69903436D1 (en) | 2002-11-14 |
AU4765999A (en) | 2000-02-07 |
DE69903436T2 (en) | 2003-06-18 |
WO2000004086A1 (en) | 2000-01-27 |
ATE225822T1 (en) | 2002-10-15 |
ES2185367T3 (en) | 2003-04-16 |
EP1098931A1 (en) | 2001-05-16 |
CA2243619A1 (en) | 2000-01-17 |
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